New study describes what happens when the brain is artificially stimulated

The research marks a step forward in the quest to develop personalized brain stimulation as a treatment for disease

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A visualization of the brain, reconstructed from MRI scans, shows tracts of white matter connecting different regions of the brain to one another. A new study that uses computational modeling to investigate brain stimulation finds that stimulating network hubs - areas of the brain that are strongly connected to other parts via white matter - results in the global activation of many brain regions. Credit: Jean Vettel, Army Research Laboratory/PLOS Computational Biology

“When a clinician has a patient with a certain disorder, how can they decide which parts of the brain to stimulate? Our study is a step toward better understanding how brain connectivity can better inform these decisions.”

Sarah Muldoon, assistant professor of mathematics

University at Buffalo

BUFFALO, N.Y. — Stimulating the brain via electricity or
other means may help to ease the symptoms of various neurological
and psychiatric disorders, with the method already being used to
treat conditions from epilepsy to depression.

But what really happens when doctors zap the brain?

Little is known about what makes this technique effective, or
which areas of the brain should be targeted to treat different
diseases.

A new study led by the University of Pennsylvania and the
University at Buffalo marks a step forward in filling these gaps in
knowledge. The research describes how the stimulation of a single
region of the brain affects the activation of other regions and
large-scale activity within the brain.

“We don’t have a good understanding of the effects
of brain stimulation,” said first author Sarah Muldoon, PhD,
assistant professor of mathematics in the University at Buffalo
College of Arts and Sciences and a core faculty member in
UB’s Computational and Data-Enabled Science and Engineering
(CDSE) Program. “When a clinician has a patient with a
certain disorder, how can they decide which parts of the brain to
stimulate? Our study is a step toward better understanding how
brain connectivity can better inform these decisions.”

“If you look at the architecture of the brain, it appears
to be a network of interconnected regions that interact with each
other in complicated ways. The question we asked in this study was
how much of the brain is activated by stimulating a single region.
We found that some regions have the ability to steer the brain into
a variety of states very easily when stimulated, while other
regions have less of an effect,” said Danielle S. Bassett,
PhD, Eduardo D. Glandt Faculty Fellow and associate professor of
bioengineering in the University of Pennsylvania School of
Engineering and Applied Science.

The research was performed in collaboration with cognitive
neuroscientist Jean M. Vettel, PhD, of the Army Research
Laboratory; control theorist Fabio Pasqualetti of the University of
California, Riverside; Scott T. Grafton, MD, and Matthew Cieslak of
the University of California, Santa Barbara; and Shi Gu of the
University of Pennsylvania Department of Psychiatry. The study was
published Sept. 9 in PLOS
Computational Biology.

The study used a computational model to simulate brain activity
in eight individuals whose brain architecture was mapped using data
derived from diffusion spectrum imaging, a type of brain image
taken by an MRI scanner. The research examined the impact of
stimulating each of 83 regions within each subject’s
brain.

While results varied by person, common trends emerged.

Network hubs — areas of the brain that are strongly
connected to other parts of the brain via the brain’s white
matter — displayed what researchers call a “high
functional effect”: Stimulating these regions resulted in the
global activation of many brain regions.

This effect was particularly notable in two sub-networks of the
brain that are known to contain multiple regional hubs: the
subcortical network (which is composed of regions that evolved
relatively early on and are critical for emotion processing) and
the default mode network (which is composed of regions that evolved
later and are critical for self-referential processing when a
person is at rest, or not completing any task).

Stimulating regions in the subcortical network culminated in
global changes, in which a diversity of areas within a
subject’s brain lit up. Stimulating regions in the default
mode network also led easily to a plethora of new brain states,
though the patterns of activation were constrained by the
brain’s underlying architecture — by the white
matter links between the nodes of the network and other parts of
the brain. Despite this limitation, the network’s agility
supports the idea that the brain at “rest” is well
suited for shifting quickly into an array of new states geared
toward completing specific tasks.

In contrast to regions within the default mode network and
subcortical networks, more weakly connected areas, such as in the
sensory and association cortex, had a more limited effect on brain
activity when activated.

These patterns suggest that doctors could pursue two classes of
therapies when it comes to brain stimulation: a “broad
reset” that alters global brain dynamics, or a more targeted
approach that focuses on the dynamics of just a few regions.

The study confirms the findings of past research by Bassett and
others on the controllability of the brain’s structural
networks. In contrast to past work that used linear modeling to
arrive at results, the new study employed nonlinear models that
more accurately reflect the brain’s complex activity, Muldoon
said.

Muldoon completed much of the research as a postdoctoral
researcher in Bassett’s lab and a contractor for the Army
Research Laboratory under civilian Jean M. Vettel. The study was
funded by the Army Research Office, the John D. and Catherine T.
MacArthur Foundation, the Alfred P. Sloan Foundation, the National
Institute of Mental Health, the National Institute of Child Health
and Human Development, the Office of Naval Research, and the
National Science Foundation.